We examined the relationship of preinjury intelligence, brain tissue volume loss, lesion location, demographic variables and a number of genetic markers to long-term cognitive decline in a group of Vietnam veterans with predominantly penetrating head injury (PHI) suffered more than thirty years ago. Using linear and stepwise regression procedures, we found that those with PHI demonstrated a greater degree of cognitive decline overall during the years following injury compared to a control group of uninjured Vietnam veterans. This became increasingly significant later in life. We also found that preinjury intelligence was the most consistent predictor of cognitive outcome across all phases of potential recovery and decline after such injuries. Laterality of lesion was not a factor. Finally, we found evidence for an association between level of cognitive decline following penetrating head injury and the possession of certain genetic markers that have been linked with brain injury and neurodegeneration. Thus exacerbated decline does occur in Vietnam veterans with PHI, is apparently unrelated to dementia and is determined by multiple factors (most notably preinjury intelligence). Post-traumatic stress disorder (PTSD) is an often debilitating mental illness that is characterized by recurrent distressing memories of traumatic events. PTSD is associated with hypoactivity in the ventromedial prefrontal cortex (vmPFC), hyperactivity in the amygdala and reduced volume in the hippocampus, but it is unknown whether these neuroimaging findings reflect the underlying cause or a secondary effect of the disorder. To investigate the causal contribution of specific brain areas to PTSD symptoms, we studied a unique sample of Vietnam War veterans who suffered brain injury and emotionally traumatic events. We found a substantially reduced occurrence of PTSD among those individuals with damage to one of two regions of the brain: the vmPFC and an anterior temporal area that included the amygdala. These results suggest that the vmPFC and amygdala are critically involved in the pathogenesis of PTSD.